The present invention relates to a composition for forming solid particles. Further, the present invention relates to a therapeutic agent, a prophylactic, or the like for periodontal diseases comprising the above composition.
Traditionally, various studies in pharmaceutics have been made for long-term sustained-release property and retention of active drugs and the like in vivo. For example, the use of solid particles, such as microspheres, nanospheres and microcapsules, can be understood as one of the forms of such studies. However, there have been pointed out some problems involved in the production of microspheres and the like, including 1) the residue of an organic solvent used to dissolve a polymer, 2) the necessity of special equipments for their production, and the like. There has, therefore, been a demand for a method capable of safely and easily preparing microspheres and the like.
In addition, various studies on pharmaceutics have been made on delivery systems for treatment of periodontal diseases. A typical example of a solid preparation is given in U.S. Pat. No. 4,764,377. The technique disclosed therein, however, poses great burdens on both physicians and patients, including time period required for administration, necessary techniques for administration, and removal of fibers after a given period of time. On the other hand, as to semi-solid preparations, there is a composition disclosed in U.S. Pat. No. 5,143,934. However, it is far from being satisfactory from the viewpoints of retention of an active drug in periodontal pockets after administration of the composition. There has, therefore, been a demand for a simple technique in which an effective concentration of the active drug can be maintained at the administration site.
Regarding the drug delivery to periodontal pockets in the treatment of a periodontal disease, some elements which have recently been regarded as pharmaceutically important include 1) administration into periodontal pockets being simple, 2) long-term retention in periodontal pockets being possible; and 3) the element acting as a carrier being biodegradable. In view of the above, one disclosed in U.S. Pat. No. 5,236,355, for example, refers to a microsphere preparation comprising an active drug. The technique disclosed herein is expensive because a complicated method known as phase separation is employed in the preparation of microspheres, making it costly, so that its clinical application seems to be difficult, in consideration of the costs involved in the present treatment of periodontal diseases. Furthermore, this preparation is in a form such that microspheres per se are administered.
Further, WO92/00718 discloses a delivery system into periodontal pockets, and U.S. Pat. No. 5,242,910 discloses an invention relating to a sustained-release composition for the treatment of a periodontal disease with nearly the same pharmaceutical characteristics as those of the aforementioned delivery system. The compositions for the treatment of a periodontal disease disclosed in these publications are all obtained in such a state of dissolving a polymer (biodegradable polymer) functioning as a sustained-release carrier in a solvent, and dissolving or dispersing an active drug in the resulting solution. When such a composition is administered, the polymer solidifies as the solvent is eluted in water, and the active drug is released. Once such a polymer solidifies, however, it retains the solid form with almost no change, resulting in the possibility that the active drug is not well distributed to the bottom of deep periodontal pockets bifurcations involvement and the like. There has, therefore, been a demand for a technique for effectively delivering an active drug to portions where drug administration is difficult.
Also, as described in U.S. Pat. No. 4,780,320, as to the preparation retained in the pocket, controlling the preparation so as not to be present in an exceeding length of time is considered to be an important factor. Therefore, in the design of a preparation, it is considered to be necessary to come up with a solution, including enlarging the surface area of the solidified polymer compound in order to increase the biodegradability of the element used as a carrier.
A first object of the present invention is to provide a composition for forming solid particles in which the administration procedures are simple, an effective concentration of the active drug can be maintained at the administration site, so that the active drug can be effectively delivered to sites difficult in administration. Still a second object of the present invention is to provide a method for safely and easily manufacturing the solid particles. Still a third object of the present invention is to provide a therapeutic agent and a prophylactic agent comprising the composition for a periodontal disease, and the like. Still a fourth object of the present invention is to provide a method of treatment and a prophylactic method effective for a periodontal disease, and the like using the above composition. These and other objects of the present invention will be apparent from the following description.
The gist of the present invention pertains to:
[1] a composition for forming solid particles comprising a biodegradable polymer, a solvent, a polyhydric alcohol, a viscosity-increasing agent, and an active drug, wherein said composition is in the form of an emulsion comprising a continuous phase rich in the polyhydric alcohol and the viscosity-increasing agent and a dispersed phase of liquid particles rich in the biodegradable polymer and the solvent, the dispersed phase being present in the continuous phase;
[2] a method for manufacturing a composition for forming solid particles, comprising adding an active drug to a mixture comprising a polyhydric alcohol and a viscosity-increasing agent and/or to a biodegradable polymer dissolved with a solvent, and mixing the mixture comprising a polyhydric alcohol and a viscosity-increasing agent, and the biodegradable polymer dissolved with a solvent;
[3] a therapeutic agent or prophylactic agent of a periodontal disease or gingivitis, comprising the composition of item [1] above;
[4] a method of treatment or prophylactic method of a periodontal disease or gingivitis comprising administering a sufficient amount of the composition of item [1] above to a periodontal pocket for the treatment or prophylaxis of a periodontal disease or gingivitis; and
[5] the use of the composition of item [1] above for manufacturing a therapeutic agent or prophylactic agent of a periodontal disease or gingivitis.